Third BNT162b2 COVID-19 Vaccine Dose Revives Humoral Response in MS Among Those Treated With Ocrelizumab, Fingolimod

New data presented at the 2022 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held October 26-28, in Amsterdam, the Netherlands, suggest that among patients with multiple sclerosis (MS) treated with ocrelizumab (Ocrevus; Genentech) or fingolimod (Gilenya; Novartis), a humoral response can be revived with the administration of a third booster dose of the BNT162b2 mRNA Covid-19 vaccine.¹

The data were compiled and analyzed by Rocco Capuano, MD, researcher, Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, and colleagues. They noted that humoral response revival occurred “independently of any demographic, clinical or laboratory variable, and confirms a good safety and tolerability profile, not only in terms of adverse events but also in terms of MS relapses.”

Previously, individuals treated with ocrelizumab and fingolimod have shown a blunted humoral response to the initial 2 doses of the BNT162b2 mRNA Covid-19 vaccine. In data published by Capuano et al in Neurological Sciences in 2021, a week after the second dose of vaccine, 100% of healthy controls mounted a significant humoral response (geometric mean 2010.4 BAU/mL; 95% 1512.7-2672.0), compared with 4 patients with MS who showed a lower response (range, <4.81-175 BAU/mL).²

In these data presented at the ECTRIMS Congress, 40 age- and sex-matched healthy controls were compared with 47 individuals with MS. Of the latter group, 28 were treated with ocrelizumab and 19 with fingolimod. Similar to the preliminary work from Capuano et al, 100% of healthy controls mounted a positive humoral response of greater than 33.8 BAU/mL at 8 weeks post vaccination, which was preserved through weeks 16 and 24 and 8 weeks prior to the third dose, as well as after the third booster dose. Comparatively, among those with MS, within 8 weeks prior to the third dose, 42.9% (n = 12) and 31.6% (n = 6) of those on ocrelizumab and fingolimod, respectively, achieved a positive humoral response. After the third booster dose, 57.14% (n = 16) and 84.2% (n = 16) of those on ocrelizumab and fingolimod, respectively, achieved this threshold.

Notably, Capuano et al wrote that “neither clinical relapses nor severe adverse events were reported in [individuals with] MS after each of the 3 doses of vaccine during the follow-up period.”

IgG antibodies to SARS-CoV-2 trimeric spike protein (anti-TSP IgG) titers among the healthy controls were significantly higher compared with those in the MS groups at all time points assessed. The healthy control group showed a significantly higher relative increase of these anti-TSP IgG levels after the booster doses with respect to the ocrelizumab (P <.001) and fingolimod (P = .032) subgroups.

Although no differences were reported at any specific time point between those in the ocrelizumab-treated and fingolimod-treated subgroups, the increase of anti-TSP IgG levels among those with MS on fingolimod was significantly higher than those in the ocrelizumab group after the third dose (P <.001). There were no prognostic sociodemographic, clinical, or laboratory variables identified for the increase of anti-TSP IgG levels between the 8 weeks prior to and after the third booster dose.

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REFERENCES
1. CapuanoR, AltieriM, ConteM, et al. Safety and efficacy of a third booster dose of BNT162b2 mRNA Covid-19 vaccine in patients with multiple sclerosis treated with ocrelizumab or fingolimod. Presented at: ECTRIMS Congress; October 26-28, 2022; Amsterdam, Netherlands. EP0929.
2. Gallo A, Capuano R, Donnarumma G, Bisecco A, Grimaldi E, Conte M, d'Ambrosio A, Coppola N, Galdiero M, Tedeschi G. Preliminary evidence of blunted humoral response to SARS-CoV-2 mRNA vaccine in multiple sclerosis patients treated with ocrelizumab. Neurol Sci. 2021;42(9):3523-3526. doi:10.1007/s10072-021-05397-7